Ornithine aminotransferase activity, liver ornithine concentration and acute ammonia intoxication
| Autor: | Genevieve Daune, Christine Grauffel, Nikolaus Seiler, Fritz Gerhart |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Ornithine
medicine.medical_specialty Orotic acid Eflornithine Arginine Administration Oral Acetates General Biochemistry Genetics and Molecular Biology Ammonia chemistry.chemical_compound Mice Oral administration Internal medicine medicine Animals Urea General Pharmacology Toxicology and Pharmaceutics Transaminases Orotic Acid biology Ornithine-Oxo-Acid Transaminase General Medicine Endocrinology chemistry Liver Enzyme inhibitor Urea cycle Creatinine biology.protein Female Injections Intraperitoneal medicine.drug |
| Zdroj: | Life sciences. 45(11) |
| ISSN: | 0024-3205 |
| Popis: | 5-Fluoromethylornithine (5FMorn) is a specific inactivator of L-ornithine:2-oxoacid aminotransferase (OAT). Inactivation of OAT causes the enhancement of L-ornithine (Orn) concentrations in all tissues. Intraperitoneal or oral administration of 10–50 mg/kg of 5FMOrn per day to albino mice rendered partial protection against lethal intoxication with 26 mmol/kg of ammonium acetate. The protective effect was maximal around 16 h after 5FMOrn administration, at the time when endogenous Orn concentrations were maximal. At this time protection by 5FMOrn against acute ammonia intoxication was comparable to that observed 1 h after the intraperitoneal administration of 10 mmol/kg of L-arginine. Pretreatment with 5FMOrn prevented the enhancement of excessive urinary excretion of orotic acid by ammonia intoxicated mice, and it enhanced urea formation in the liver. These biochemical effects demonstrate that 5FMOrn shifts Orn into the urea cycle, Orn which normally would be transaminated. Since even long-term treatment of mice with 5FMOrn did not reveal toxic effects, this compound may be considered for the treatment of certain conditional deficiencies of Orn or arginine. |
| Databáze: | OpenAIRE |
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